Peripheral Vasodilation in Obese Humans

肥胖人群的外周血管舒张

基本信息

  • 批准号:
    8515512
  • 负责人:
  • 金额:
    $ 52.34万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-09-01 至 2016-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this research program is to investigate the obesity-related changes in microvascular function that initiate the cardiovascular disease process. The growing population of obese adults is predicted to create a large public health burden in the next few decades. Skeletal muscle accounts for the majority of peripheral resistance and glucose uptake in humans. Decreased muscle vasodilation likely contributes to hypertension and sets the stage for hyperglycemia-both hallmarks of metabolic syndrome and diabetes. Thus, low muscle blood flow in obese humans may contribute to reduced exercise capacity-this in turn sets the stage for development of long-term cardiovascular diseases like diabetes. We propose to study younger obese "metabolically health" adults (18-35 yrs), without confounding effects of age, metabolic syndrome, or diabetes- before the negative effects of obesity can exert their full negative impact. The general hypothesis is that obesity impairs endothelium dependent dilation (EDD) and exercise vasodilation via increased reactive oxygen species (ROS) and reductions in vasodilator signals and increased vasoconstrictor signals. Our preliminary data suggest young obese adults exhibit reduced EDD and exercise vasodilation, and acute ROS scavenging improves both. We will test our hypotheses by arterial drug infusion to test EDD mechanisms in lean and obese humans. We will use similar approaches to test vascular mechanisms controlling blood flow during dynamic exercise. Next, we will test EDD and exercise vascular responses before and after a diet and exercise intervention, where we can parcel out whether physical activity or weight loss plays a larger role in vascular improvements. Finally, we will sample artery endothelial cells from these same subjects to identify molecular pathways that change with obesity as potential therapeutic targets. These studies integrate physiologic, pharmacologic, and molecular approaches to test our hypotheses. We have several exciting preliminary findings that support our hypotheses, and have designed a complementary set of Aims the will soundly address our research questions. A multi-disciplinary, state-of-the-art approach will be used to pursue these aims, which will provide fundamental mechanistic understanding of EDD and exercise mechanisms responsible for reduced blood flow in obese humans. Our novel findings will guide the development of novel therapeutic strategies for obesity and other diseases, including obstructive sleep apnea, metabolic syndrome and diabetes.
描述(由申请人提供): 这项研究计划的总体目标是调查肥胖相关的微血管功能的变化,启动心血管疾病的过程。预计在未来几十年内,肥胖成年人的不断增长将造成巨大的公共卫生负担。骨骼肌占人体外周阻力和葡萄糖摄取的大部分。肌肉血管舒张功能下降可能导致高血压,并为高血糖症奠定基础,这两种症状都是代谢综合征和糖尿病的标志。因此,肥胖人群的低肌肉血流量可能会导致运动能力降低,这反过来又为糖尿病等长期心血管疾病的发展奠定了基础。我们建议研究年轻的肥胖“代谢健康”的成年人(18-35岁),没有年龄,代谢综合征或糖尿病的混杂影响-在肥胖的负面影响可以发挥其全部负面影响之前。一般的假设是肥胖通过增加活性氧(ROS)和减少血管舒张信号和增加血管收缩信号损害内皮依赖性舒张(EDD)和运动血管舒张。我们的初步数据表明,年轻的肥胖成年人表现出减少EDD和运动血管舒张,急性ROS清除改善两者。我们将通过动脉药物输注来测试我们的假设,以测试瘦和肥胖人群中的EDD机制。我们将使用类似的方法来测试在动态运动过程中控制血流的血管机制。接下来,我们将测试饮食和运动干预前后的EDD和运动血管反应,在那里我们可以划分出体力活动或减肥是否在血管改善中发挥更大的作用。最后,我们将从这些相同的受试者中采集动脉内皮细胞样本,以确定随肥胖而变化的分子途径作为潜在的治疗靶点。这些研究整合了生理学、药理学和分子学方法来验证我们的假设。我们有几个令人兴奋的初步发现,支持我们的假设,并设计了一套互补的目标,将健全地解决我们的研究问题。一个多学科,国家的最先进的方法将被用来追求这些目标,这将提供基本的机械理解的EDD和运动机制负责减少肥胖的人的血流量。我们的新发现将指导肥胖和其他疾病的新治疗策略的开发,包括阻塞性睡眠呼吸暂停,代谢综合征和糖尿病。

项目成果

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WILLIAM G SCHRAGE其他文献

WILLIAM G SCHRAGE的其他文献

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{{ truncateString('WILLIAM G SCHRAGE', 18)}}的其他基金

Human cerebral blood flow regulation: sex, mechanism, and stress differences
人类脑血流调节:性别、机制和应激差异
  • 批准号:
    10650368
  • 财政年份:
    2020
  • 资助金额:
    $ 52.34万
  • 项目类别:
Human cerebral blood flow regulation: sex, mechanism, and stress differences
人类脑血流调节:性别、机制和应激差异
  • 批准号:
    10407466
  • 财政年份:
    2020
  • 资助金额:
    $ 52.34万
  • 项目类别:
Insulin resistance, cognitive health, and perfusion of the adolescent brain
胰岛素抵抗、认知健康和青少年大脑灌注
  • 批准号:
    9980475
  • 财政年份:
    2019
  • 资助金额:
    $ 52.34万
  • 项目类别:
Peripheral Vasodilation in Obese Humans
肥胖人群的外周血管舒张
  • 批准号:
    8185406
  • 财政年份:
    2011
  • 资助金额:
    $ 52.34万
  • 项目类别:
Peripheral Vasodilation in Obese Humans
肥胖人群的外周血管舒张
  • 批准号:
    8688332
  • 财政年份:
    2011
  • 资助金额:
    $ 52.34万
  • 项目类别:
Peripheral Vasodilation in Obese Humans
肥胖人群的外周血管舒张
  • 批准号:
    8323220
  • 财政年份:
    2011
  • 资助金额:
    $ 52.34万
  • 项目类别:
Aging and Microvascular Dysfunction in Human Skeletal Muscle
人体骨骼肌的衰老和微血管功能障碍
  • 批准号:
    7587863
  • 财政年份:
    2009
  • 资助金额:
    $ 52.34万
  • 项目类别:
Aging and Microvascular Dysfunction in Human Skeletal Muscle
人体骨骼肌的衰老和微血管功能障碍
  • 批准号:
    7770776
  • 财政年份:
    2009
  • 资助金额:
    $ 52.34万
  • 项目类别:
Muscle Pump and Chemical Dilation in Exercise Hyperemia
运动充血中的肌肉泵和化学扩张
  • 批准号:
    6710162
  • 财政年份:
    2002
  • 资助金额:
    $ 52.34万
  • 项目类别:
Muscle Pump and Chemical Dilation in Exercise Hyperemia
运动充血中的肌肉泵和化学扩张
  • 批准号:
    6447034
  • 财政年份:
    2002
  • 资助金额:
    $ 52.34万
  • 项目类别:

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